System and method for cytopathological and genetic data based treatment protocol identification and tracking

ABSTRACT

A method of assessing a target including collecting patient data, identifying a target in an image dataset, preparing a pathway plan to arrive at the target, inserting a medical instrument and following the pathway plan to arrive at the target from an opening, extracting a first biopsy sample from the target, performing a cytopathological examination on the biopsy sample, collecting genetic information from the biopsy sample, and presenting one or more treatment options based on a correlation of the patient data, the cytological examination, and the genetic information of the first biopsy sample, and their comparison to the patient data, cytological examination and genetic information of previously acquired biopsy samples. The method may further include acquiring a second biopsy sample.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalApplication Ser. Nos. 62/097,690, 62/097,697, 62/097,713, and62/097,721, all of which were filed on Dec. 30, 2014. This applicationis related to U.S. patent application Ser. Nos. ______, ______, and______, all of which were filed on Oct. 29, 2015. The entire contents ofeach of the above applications are hereby incorporated herein byreference.

BACKGROUND

1. Technical Field

The present disclosure relates to systems and methods for retrieving abiopsy sample, obtaining cytopathological information about the biopsysample, obtaining genetic information about biopsy sample, identifying atreatment course, performing the treatment, observing the effects of thetreatment course on the target from which the biopsy sample was taken,and maintaining an updating a database correlating each of these typesof data.

2. Description of Related Art

A common device for inspecting the airway of a patient is abronchoscope. Typically, the bronchoscope is inserted into a patient'sairways through the patient's nose or mouth and can extend into thelungs of the patient. A typical bronchoscope includes an elongatedflexible tube having an illumination assembly for illuminating theregion distal to the bronchoscope's tip, an imaging assembly forproviding a video image from the bronchoscope's tip, and a workingchannel through which instruments (e.g., diagnostic instruments such asbiopsy tools or therapeutic instruments such as ablation catheters) canbe inserted.

Bronchoscopes, however, are limited in how far they may be advancedthrough the airways due to their size. Where the bronchoscope is toolarge to reach a target location deep in the lungs a clinician mayutilize certain real-time imaging modalities such as fluoroscopy.Fluoroscopic images, while useful present certain drawbacks fornavigation as it is often difficult to distinguish luminal passagewaysfrom solid tissue. Moreover, the images generated by the fluoroscope aretwo-dimensional whereas navigating the airways of a patient requires theability to maneuver in three dimensions.

To address these issues, systems have been developed that enable thedevelopment of three-dimensional models of the airways or other luminalnetworks, typically from a series of computed tomography (CT) images.One such system has been developed as part of the ILOGIC®ELECTROMAGNETIC NAVIGATION BRONCHOSCOPY® (ENB™), system currently soldby Covidien LP. Such systems are generally referred to aselectromagnetic navigation or EMN systems. The details of such a systemare described in the commonly assigned U.S. Pat. No. 7,233,820, filed onMar. 29, 2004 by Gilboa and entitled ENDOSCOPE STRUCTURES AND TECHNIQUESFOR NAVIGATING TO A TARGET IN BRANCHED STRUCTURE, the entire contents ofwhich are incorporated herein by reference.

Regardless of whether using a bronchoscope or an EMN system, uponidentification of a tumor, mass, or other area of interest a clinicianwill generally take a biopsy in order to conduct pathology testing. Theresult of the pathology will identify whether the tumor or area ofinterest is cancerous, and will drive the next steps that a clinicianwill undertake with respect to that patient. The present disclosure isdirected to systems and methods to assist the clinician in determiningthose next steps.

SUMMARY

In an aspect of the present disclosure a method of assessing a target isprovided. The method includes collecting patient data, identifying atarget in an image dataset, preparing a pathway plan to arrive at thetarget, inserting a medical instrument and following the pathway plan toarrive at the target from an opening, extracting a first biopsy samplefrom the target, performing a cytopathological examination on the biopsysample, collecting genetic information from the biopsy sample, andpresenting one or more treatment options based on a correlation of thepatient data, the cytological examination, and the genetic informationof the first biopsy sample, and their comparison to the patient data,cytological examination and genetic information of previously acquiredbiopsy samples. Additionally, or alternatively, the method may furtherinclude acquiring a second biopsy sample, performing a cytologicalexamination on the second biopsy sample, collecting genetic informationof the second biopsy sample, and presenting one or more treatmentoptions based on a correlation of the patient data, the cytologicalexamination, and the genetic information of the second biopsy sample,and their comparison to the patient data, cytological examination andgenetic information of previously acquired biopsy samples.

The presentation of the treatment options may include presentation ofthe details of the first biopsy sample including one or more of theimages from the image dataset, the cytopathological examination results,and the genetic information. The prior biopsy sample may be from thesame target or from different targets in the same patient or from otherpatients.

The correlation may identify a similarity in the cytological examinationresults of the first biopsy sample and the previously acquired biopsysamples. Additionally, or alternatively, the correlation may identify asimilarity of gene mutation of the first biopsy sample and thepreviously acquired biopsy samples. Additionally or alternatively, thecorrelation may identify a similarity of one or more of cytologicalexamination results, a gene mutation, age, ethnicity, sex, infirmity ofpatient, location of the target, and/or observed outcomes in the firstbiopsy sample and the previously acquired biopsy samples.

The presented treatment options may include the standard of care,clinical trials, investigational treatments, and/or combinationsthereof. Additionally, or alternatively, the presented treatment optionsmay include an expected outcome based on observed outcomes stored in thedatabase related to the prior biopsy samples used in the correlation.Additionally, or alternatively, the presented treatment options mayinclude treatment details including one or more of power, intensity,dosage, duration, number of cycles, treatment regimen, co-treatments,and timing of each. Additionally, the presented treatment options may beaccessible to a care team via a network.

The database may store any or all of the patient data, the image data,the cytological examination results, and the genetic information in adatabase accessible via a network. In one aspect, upon selecting atreatment option, the selected treatment option is stored in thedatabase. Additionally, or alternatively, upon executing the selectedtreatment, the treatment details may be stored in the database includingone or more of power, intensity, dosage, duration, number of cycles,treatment regimen, co-treatments, and timing of each.

In an aspect, the method further includes observing the outcome of theselected treatment and storing data related to the outcome in thedatabase. Further, following observation of the outcome of the selectedtreatment, the data stored in the database for the patient is availableto others for conducting a different correlation for a biopsy sampletaken from a different patient. Observing the outcome may includegenerating a second image data set at storing the second image data setin the database. The second image data set may depict one or moremarkers placed in the patient during the biopsy extraction.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of the present disclosure are described hereinbelow withreference to the drawings, wherein:

FIG. 1 is a flowchart depicting a method in accordance with the presentdisclosure;

FIG. 2 is a schematic of a pathway planning device in accordance withthe present disclosure;

FIG. 3 is an Electromagnetic Navigation system in accordance with thepresent disclosure;

FIG. 4 is a computer network in accordance with the present disclosure;

FIG. 5 is a sample database in accordance with the present disclosure;and

FIG. 6 is a sample web page in accordance with the present disclosure.

DETAILED DESCRIPTION

The present disclosure is directed to an integrated approach for targetbiopsy, cytopathology, gene profiling or gene mapping, target treatment,outcome tracking, biologically targeted therapy, immunotherapy, externalor internal radiation therapies, or any combinations thereof. Oneembodiment of the present disclosure is directed to aggregating datafrom large numbers of biopsies including data relating to each biopsy'scytopathology and its genetic profile. Re-biopsy data in which a second,third, etc., biopsy is taken of the same target at different times toassess changes in pathology, genetic profile, and other characteristicdata is also collected. Treatment data is also collected and correlatedto the biopsy data in instances where treatment is undertaken. Thetreatment data may include the manner of treatment (e.g., chemotherapy,ablation, resection, biologically targeted therapy, immunotherapy,external or internal radiation therapies, etc.) as well as more specificdata such as duration and power levels of ablation, dosages ofchemotherapeutic drugs, drug combinations, combined surgical and drugtreatments, etc. Further, outcomes are monitored, both positive andnegative, as a result of the treatment. As this data is collected and agreater number of genetic profiles are identified and associated withtreatments and patient outcomes, predictive models are developed whichcan provide a clinician with a variety of treatment options tailored tothe specific individual expressing a particular type of genetic profilein their particular tumor at a particular time in the progression oftheir disease.

One embodiment of the present disclosure is depicted in FIG. 1 whichshows a method 100 for assessing and treating a patient and forcollecting data to enable correlation of treatment with disease andgenerate predictive outcomes for a particular patient. At step 102,imaging is conducted of the patient, for example, Computer Tomography(CT) imaging, Magnetic Resonance imaging (MRI), fluoroscopy, x-ray orother imaging modalities. Other imaging modalities may be employedwithout departing from the scope of the present disclosure.

Once the images, for example CT images, have been generated, they may beimported into a pathway planning system 200 (FIG. 2) as described inco-pending and commonly assigned U.S. patent application Ser. No.13/838,805 entitled PATHWAY PLANNING SYSTEM AND METHOD, the entirecontents of which are incorporated herein by reference. The pathwayplanning system 200 may be embodied on a laptop, desktop, tablet, orother similar device, having a display 202, memory 204, one or moreprocessors 206 and/or other components of the type typically found in acomputing device. The pathway planning system may also be part of a thinclient distributed network system wherein the data is stored remotely inmemory 204 located on one or more servers, for example in the cloud, thesoftware being executed by the processors 206 is stored and executedremotely on the one or more servers, and the display 202 and a userinput such as a keyboard or mouse are the primary local components. Aswill be understood by those of skill in the art some local processingwill also be necessary to receive, transmit, and manipulate data, forexample for the display 202. Display 202 may be touch sensitive and/orvoice activated, enabling display 202 to serve as both an input andoutput device. Alternatively, a keyboard (not shown), mouse (not shown),or other data input devices may be employed.

Memory 204 may be any non-transitory, computer-readable storage mediafor storing data and/or software that is executable by processor 206 andwhich controls the operation of the pathway planning system 200. Pathwayplanning system 200 may also include a network module 208 connected to adistributed network or the internet via a wired or wireless connectionfor the transmission and reception of data to and from other sources.For example, computing device 200 may receive computed tomographic (CT)images of a patient from a server, for example, a hospital server,internet server, or other similar servers, for use during pathwayplanning. Patient CT images may also be provided to pathway planningsystem 200 via a removable memory e.g., a USB drive (not shown).

A pathway planning module 210 includes a software program stored inmemory 204 and executed by processor 206 of the pathway planning system200. As described in greater detail in the incorporated U.S. patentapplication Ser. No. 13/838,805, pathway planning module 210 guides aclinician through a series of steps to develop a pathway plan for lateruse during a medical procedure. Pathway planning module 210 communicateswith a user interface module 211 displaying visual interactive featuresto a clinician on the display 202 and for receiving clinician input.

Using the tools of a pathway planning system 200, and particularly thepathway planning module 210, images, such as CT images, can be retrievedfrom memory 204 and reviewed on display 202 by a clinician at step 104.During review, if an area of interest is identified (step 106) this areaof interest can be marked electronically in the image data andidentified as a target. Either after identifying a target, or followingcomplete review of all the image data and identification of all thetargets, the method 100 can proceed to step 110 where a pathway planfrom the area(s) of interest to a natural body opening, or a surgicalbody exit point (e.g., an incision) can be generated and stored in adatabase 500 (shown in FIG. 5) and associated with the patient.

If no areas of interest are identified in step 106, the image datacollected in step 102 may be stored in a database 500, if not alreadystored therein, at step 108 and associated with the patient forcomparison to later image data acquired of the same patient in order toassess changes in the patient over time. The database 500 may be storedlocally on the pathway planning system 200 or remotely on a server 212which is accessible via the network module 208, as shown in FIG. 4. Aswill be described in greater detail below, the image data as well asother relevant data of the patient are made available via database 500for research and analysis by other clinicians for assessing their ownpatient's disease and treatment options. For example, some or all of thedata stored in database 500 may be openly accessible for otherphysicians, clinicians, or researchers to access to assist in globaltreatment decision support.

Imaging and review steps 102 and 104 may be undertaken as part of anoutcome monitoring step 138, described below. As a result, the imagingundertaken in step 102 may be undertaken and compared in review step 104with prior imaging stored in the database 500 to determine whether priortreatments were successful, whether prior determinations of proceedingwith “watchful waiting” are no longer appropriate, whether the diseasehas changed in some observable way (e.g., increased in size), and/orother changes in patient and disease state known to those of skill inthe art and relevant to the observation, management and treatment of thedisease.

Following generation of a pathway plan in step 110, the pathway plan canbe reviewed by the clinician in step 112 and must be accepted by theclinician at step 114. If the pathway is not acceptable, the cliniciancan reject the plan and the pathway planning module 210 returns to step108. The clinician can then utilize the tools of the pathway planningmodule 210 to generate a new pathway, or alter the existing pathway to amore desirable route. Once the pathway plan has been accepted in step114 the pathway plan is stored in memory 204 and is ready for export foruse in an Electromagnetic Navigation System 300 (EMN) depicted in FIG.3. The pathway plan may be exported to the EMN system 300 using aportable memory such as a USB drive, or the memory 204 may be located onthe server 212 as shown in FIG. 4 and accessible to both the pathwayplanning system 200 and the EMN system 300.

EMN system 300 may be the ELECTROMAGNETIC NAVIGATION BRONCHOSCOPY®system currently sold by Covidien LP. Typically the EMN system 300includes a bronchoscope 302, one or more of two different types ofcatheter guide assemblies 304 and 306, monitoring equipment 308, anelectromagnetic field generator 310, a tracking module 312, and acomputer system 314. FIG. 3 shows a patient “P” lying on an operatingtable 316 including an electromagnetic field generator 310. Placed onthe patient “P” are a number of sensors 315, whose position in themagnetic field generated by the electromagnetic field generator 310 canbe determined by the tracking module 312.

Each of the catheter guide assemblies 304, 306 includes an extendedworking channel 318 that is configured to receive a locatable guidecatheter 320 which includes a sensor 322. The locatable guide catheter320 is electrically connected to the EMN system 300, and particularly,the tracking module 312 enables navigation and tracking of the sensor322 within a luminal network, such as the lungs of a the patient “P,” toarrive at a designated target. The extended working channel (EWC) 318 isconfigured to receive instruments including the locatable guide catheter320 and sensor 322, biopsy tools (not shown) and a microwave ablationcatheter 324, as well as others without departing from the scope of thepresent disclosure. A locking mechanism 321 ensures that the locatableguide catheter 320 and the extended working channel 318 move in concert.Each catheter guide assembly 304, 306 includes a handle 315 to enablemovement and navigation through a luminal network such as the lungs of apatient “P.”

As shown in FIG. 3, the microwave ablation catheter 324 is electricallyconnected to a microwave generator 326 via a feedline 328. The generator326 supplies microwave energy to the catheter to treat tumors andlesions within the patient “P.” A cooling circuit 330 cools themicrowave ablation catheter 324 as is commonly known in the art toprevent damage to equipment and the patient except in those locations tobe treated.

Stored on or accessible from the computer system 314 is navigationsoftware enabling the navigation of one or more tools into the patient Pfollowing the pathway plan developed in steps 110-114. One suchnavigation software is described in detail in U.S. Provisional PatentApplication No. 62/020,240 filed Jul. 2, 2014 by Brown, et al. andentitled SYSTEM AND METHOD FOR NAVIGATING WITHIN THE LUNG, the entirecontents of which are incorporated herein by reference.

As described in the '240 application, the sensor 322 detects a magneticfield generated by the electromagnetic field generator 310, and thetracking module 312 is able to identify the sensor's location within themagnetic field. The patient's location within the magnetic field, andparticularly those portions of the patient which were previously imaged,are registered with the previously acquired images and the pathway planimported to computer system 314. As a result, the navigation softwarestored on or accessible from the computer system 314 is capable ofdepicting a representation of the location of the sensor 322 within thepatient P. This representative location may be in reference to renderedCT images or in reference to a 3D model generated from the CT image dataor other types of images as described in the '240 application.

Once the pathway plan is imported to the EMN system, and particularlycomputer system 314, a clinician is able perform EMN in step 120 tofollow the pathway plan by manipulating the catheter guide assembly 304,306, through the bronchoscope 302. The location of the sensor 322 withinthe patient “P” is depicted to the clinician on the images and/or 3Dmodel of the luminal network of the patient, and the pathway to thetarget is shown in the user interface of the computer system 314. Theclinician is able to manipulate the catheter guide assembly 304, 306until the sensor 322 is proximate the target identified in step 106.

In embodiments involving re-biopsy (i.e., re-evaluating a target thathas been previously been biopsied) it is possible to follow the samepathway plan used to access the target initially. However, given therelatively small cost of imaging, it is contemplated that typicallyclinicians will undergo a new imaging process 102 and pathway planningsteps 110-116, each time a biopsy is contemplated. Changes to the targetover time (either with or without treatment) and the need to confirmnavigation to the appropriate location in view of these changes maynecessitate a new imaging process 102 be undertaken.

Having arrived at the target location, the clinician can remove thelocatable guide catheter 320 from the extended working channel 318. Thismay not be necessary if the sensor 322 is located on the extendedworking channel, as is also contemplated by the present disclosure.Regardless, having arrived at the target, as part of step 120, one ormore biopsy samples will be taken of the target. The location from whichthe samples were taken may be electronically recorded in a navigationfile as part of step 121. A navigation file is a computer record whichmay include both the pathway plan and the actual navigation steps takenduring the EMN. A graphic representation of the biopsy (e.g., anelectronic marker) may be placed by in the navigation file, anddisplayed to the clinician on the user interface of the computer system314. In addition to a graphic representation of the biopsy, anelectronic marker may include annotations denoting specific biologicaldata such as, for example, tumor type and subtype, cytology andhistology test results data, genomic/proteomic data, resistance data,etc. Additionally, the annotations may co-note anatomical detailsincluding, for example, distance to airway, fissure, vascularity, etc.

In addition to electronic markers, physical fiducial markers may beplaced at or near each of the biopsy sites. These markers ease findingthe target in future CT scans and other imaging techniques and make iteasier to revisit the target at a later date in a subsequent EMNprocedure and for performing re-biopsy as may be necessary in theoutcome monitoring steps described below.

After taking a biopsy at a target and placing markers at the target, theclinician returns to the pathway plan. Following reinsertion of thelocatable guide catheter 320 with sensor 322 the clinician proceeds tonavigate to the next target. Again samples are taken of this and everytarget until all the targets have been navigated to, electronicallymarked, biopsies taken and physical markers placed at the targets. Asnoted above, in instances where the EWC 318 includes sensor 322,reinsertion of the locatable guide catheter 320 is unnecessary.

With each biopsy, cytopathology must be undertaken at step 122 todetermine the disease state of the cells recovered from the target inthe biopsy. The results of the cytopathology have at least two uses.First the results of cytopathology identify whether the individualpatient has cancer and the type of cancer; another disease, or whetherthe target is a benign growth. Second, each biopsy represents a datapoint to be incorporated into a potential treatment database 500 andpredictive outcome models generated from the database 500, as will bedescribed in greater detail below.

Cytopathology may be performed using a rapid on-site evaluation (“ROSE”)for immediate testing. Thus, in some instances the testing may beperformed even before the clinician moves on to the next targetfollowing the extraction of a biopsy. In some instances, this ensuresthat sufficient samples are taken from each target for the biopsy,allowing the clinician to repeat the biopsy immediately, if needed. Inaddition, in some instances, use of ROSE procedures enables theclinician to perform immediate treatment of the target without the needfor a subsequent EMN, thus streamlining the treatment process andreducing the number of procedures and time between procedures for thepatient. The results of cytopathology are stored in a database 500,shown in FIG. 5, in step 124. This data is available to the clinicianfor treatment and monitoring of the specific patient “P,” as well as foruse in comparison to other patients to identify treatment options andpredicting outcomes, as will be described in greater detail below.Additionally the cytopathology may be part of a point of care, (e.g.,bedside sequencing system) enabling even faster analysis of biopsysamples and interconnectivity with the systems and methods describedherein.

Cytopathology may be part of the continuum of care as part of an outcomemonitoring step 138 described below. As a result, the cytopathology maybe taken and compared with prior cytopathological results to determinewhether prior treatments were successful, whether prior determinationsof proceeding with “watchful waiting” is no longer appropriate, whetherthe disease state has advanced from the last cytopathological testing orwhether the disease has become resistant to the prior treatments, aswell as other determinations.

With the cytopathology undertaken at step 122, either serially (asshown) or in parallel, genetic testing can be undertaken in step 126.The genetic testing may reveal a gene profile or gene mapping of thebiopsy samples, or other information. The gene profile or gene mappingmay express a mutation of a gene, for example the biopsy in question maybe positive for mutations in the epidermal growth factor receptor(EGFR), anaplastic lymphoma kinase (ALK) mutations, and Kirsten ratsarcoma (KRAS) and other rat sarcoma (RAS) family member mutations, aswell as other genetic markers known to those of skill in the art. Eachof these mutations, as well as other genetic makers, is associated withand has been observed in a variety of cancers. The gene profiling orgene mapping is conducted in step 126, and the data is stored indatabase 500 in step 128. In step 126, genetic testing is undertaken foreach target identified in the pathway planning step 110-114 as differenttargets may express different or no mutations despite occurring in thesame patient. As will be recognized by those of skill in the art,genetic profiling of the type contemplated here requires use ofspecialized laboratory facilities and may require some time to perform.As such, there may be a delay between the steps of performing the biopsyin step 120, conducting cytopathology and gene profiling in steps 122and 126, and the subsequent steps of the method 100. Current technologyenables results to be processed in as fast as 24 hours, but it iscontemplated that as technology develops real-time gene profiling willbe developed enabling a real-time on site gene profiling, and furtherstreamlining the process of identification and treatment of the disease.

As with imaging and cytopathology, genetic mapping of a biopsy samplemay be part of the continuum of care as part of an outcome monitoringstep 138 described below. As a result, the genetic map may be taken andcompared with prior genetic maps to determine whether prior treatmentswere successful, whether prior determinations of proceeding with“watchful waiting” is no longer appropriate, or whether the disease hasfurther mutated in some fashion. Again, each of these genetic mappingsis stored in the database 500.

Genetic mapping data may not be solely limited to genetic mapping toparticular locations of cancer (e.g., lung, liver, stomach, etc.).Rather, if available, database 500 may include data for a varietycancers, many of which are completely unrelated to the individualpatient “P.” While not typically considered for treatment, where a tumorin the lung of patient “P,” for example, expresses the same mutation asone take from a different patient's liver that data may prove useful indetermining the treatment options for the patient “P.” As a result, thetreatment of patient “P,” as will be discussed below may bear a closerresemblance to a liver cancer treatment protocol than a typical lungcancer treatment protocol. For example, if microwave ablation is thedesired treatment regimen, the power and duration settings for theablation may be more closely associated with the liver cancer treatmentsettings in view of this genetic mapping, where that type of treatmenthas proven effective in the treatment of liver cancer. Othercorrelations of data from genetic profiles and cytopathology from aspecific biopsy sample are enabled by the collection andcross-referencing of the data in database 500.

In step 130, the clinician may employ the computer system 314 to accessthe database 500, which may be stored either locally or on server 212,to compare the patient “P” data with other individuals who have beenpreviously treated. Alternatively, the clinician may use any computingdevice 402 capable of accessing the network 400, and specifically theserver 212 as shown in FIG. 4. This enables the clinician to conduct theEMN, collect the biopsy samples, have cytopathology and genetic testingperformed, and subsequently review the aggregated results for thatpatient “P” at a later date. The computing device 402 may be a laptop,tablet, smart phone, desk top computer, or any other network enableddevice.

By cross referencing genetic profile or gene mapping withcytopathological information relating to the existence of cancer, andmore importantly a specific type of cancer, and further with data suchas age, sex, race, location of the cancer, medical history of thepatient, specified standard of care, type of treatment undertaken, andobservation of the outcomes the fields of database 500 can be filledwith actual data from an ever increasing population of patients. Thisdata is then accessible to clinicians when treating specific patients aswell as for further analyses in order to determine correlations betweenthe data, identify potential outcomes of different treatments for groupsand types of patients, and to develop revised protocols for the standardof care. Effectively, with enough patient data, greater and greaterpredictive capability can be made available to the clinician for use indetermining the best course of action for the particular patient “P”seeking treatment.

In one embodiment of the present disclosure, the server 212 is aweb-server enabling access via the internet. Further, the web-server 212runs software presenting a series of web pages to the clinician via theconnection to computer system 314 or device 402, one such web-page isshown in FIG. 6. Other web pages presented via the software running onsever 212 may include those depicted in incorporated by reference U.S.Patent Provisional and Utility Application No. 62/020,240 and Ser. No.13/838,805.

FIG. 6 is an exemplary web page 600 displaying in step 132 the result ofthe analysis step 130 determining the cytological and/or gene profileanalogues for the patient “P.” Web page 600 provides an analysis of thespecific patient “P” data in comparison with that stored in database 500of other patients whose samples have been collected and analyzedpreviously. Web page 600 identifies the patient name and medical recordnumber of that patient as well as the identity of the care team for thatpatient “P.” Web page 600 includes a number of fields which can bepopulated using a combination of data from the database 500 relating tothe specific patient “P,” data generated based on the comparison of thepatient's data and the data of other patients having some level ofsimilarity, and data retrieved from other databases.

On web page 600, a results banner 602 may be used to provide an overviewof the diagnosis for a patient “P.” As shown in FIG. 6, this overview isan identification of the type of cancer identified by the pathologist,for example an Adenocarcinoma. Below the results banner 602 are a seriesof fields of data relating to the patient “P.” Each field has a tab 604presenting one each for “imaging,” “pathology,” “molecular,” and“function.” Other tabs 604 may be presented without departing from thescope of the present disclosure. Next to each of these tabs is a summaryof the contents to be found in the database 500 for the patient “P”related to each tab 604. For imaging, the size and location of thetarget are identified. For pathology the type of cancer and otherinformation from the cytopathology are presented. Next to the tab 604labeled molecular are the results of the genetic profiling or testing,e.g., the identification of a mutation. Next to the tab labeled functionis an assessment of other factors relating in this example to lungfunction of the patient “P.” Other tabs may include an assessment of thepatient's ability to withstand the rigors of treatment options (e.g.,chemotherapy, radiation, and/or surgery), as well as other data aboutthe patient.

A further field 606 depicts a representative image of the target 608 tobe treated. By clicking on the image or on the neighboring imagingbutton 604, the web-page 600 may reveal a new window or web pagedisplaying the CT image data or present the image data in the form asseen in the pathway planning module 210. This review of the CT imagedata enables the clinician to orient themselves with respect to thetarget and confirm information about the target 608. Similarly, byclicking or selecting any of the buttons 604, the clinician may bepresented with a new web-page including detailed information from thedatabase 500 for the individual patient “P.”

Field 610 in FIG. 6 presents treatment options that are available forthe patient “P.” These treatment options may include the “standard ofcare,” which is typically considered the treatments that are accepted bymedical experts as a proper treatment for a certain type of disease andthat are widely used by healthcare professionals. This is also calledbest practice, standard medical care, and standard therapy. The standardof care may be set by, for example, the National Cancer Institute at theNational Institutes of Health or by a local or regional governing bodyfor a particular practice of medicine. The standard of care for aparticular cancer will depend on size, location, and dispersion and mayinclude resection, lobectomies, radiation, radiosurgery, chemotherapy,targeted therapies, photodynamic therapy, electrocautery, biologicallytargeted therapy, immunotherapy, external or internal radiationtherapies, and others as well as ordered combinations of thesetreatments.

While the standard of care for a particular disease is the recommendedcourse of action, clinicians will immediately recognize that there maybe reasons not to follow the standard of care. For example, if thestandard of care for a particular disease is surgery, but the patient isold and infirm and might be incredibly stressed by the surgery, aclinician in consultation with the patient may decide the standard isnot appropriate for that particular patient. To assist in theseinstances, field 610 may also identify whether there are existing“clinical trials” on-going which may be of interest to the clinician andin which the patient may wish to participate in order to receivedevelopmental treatments. These clinical trials can be very important topatients, particularly if it is deemed that the standard of care has notbeen effective or is otherwise undesirable. A further option is theavailability of investigational treatments, for example, through theU.S. Food and Drug Administration's Expanded Access (compassionate use)programs. These are typically the same therapies available to thepatient via the clinical trials, but do not require participation in thetrial, and do not run the risk of receiving the placebo that is commonfor a portion of the trail members. Selecting on the web page 600 one ofthe specified treatment options in field 610 will provide the clinicianwith more information regarding the details of that option.

Some of the details of the treatment options available to the clinicianusing the system described herein are only available as a result of thecollection, cross-referencing and sorting of the data in the database500. As a result of the previously collected data, including datarelating to the selected treatment for patients as well as the observedoutcomes, described in greater detail below, which is collected, stored,and cross referenced in database 500, a clinician is given ever moregranular data to compare to the patient “P” and provide diagnosis andprognosis information. The increased granularity or particularity ofinformation including the cytopathology, gene profiling, treatmentoptions and observed treatment outcomes allow the clinician and thepatient to develop the personalized plan for treatment depicted in FIG.6 as filed 612. A further field depicted on web page 600 is thepersonalized plan 612. This personalized plan displays the course ofaction that is decided upon in consultation with the patient “P,” andthe care team on how to treat the particular patient after consideringall of the information described hereinabove.

As will be appreciated by those of skill in the art, data in thedatabase 500 (including imaging, navigation, biopsy, genetic, etc.) maybe stored individually, and/or annotated as composite report together,including overlaid on imaging data set. In addition, follow-up biopsies,and the data associated with them, may be overlaid by time course forlongitudinal studies (seeing results/outcomes over time); one patient oraggregated patient pools. The data in the database 500 may be used todevelop new clinical trials. In at least one embodiment of the presentdisclosure the data in the database 500 may be presented in an opensource format for other physicians or clinicians to access and inform abroader body of clinicians on treatment options, decisions, andpredictive outcomes.

In one embodiment the personalized plan, and the recommended series ofactions depicted in field 612 are generated by software running on theserver 212. In such a scenario, the software compares the data indatabase 500 and identifies a sufficient number of analogues for thepatient “P” based on all of the available data. The identifiedanalogues' treatment options are then compiled and those with anoccurrence interval above a predetermined threshold may be selected bythe software. Alternatively, a selected number of the most commonlyapplied treatments may be selected by the software. In anotheralternative, all selected treatments are ranked based on the observedpatient outcome, and those with the best outcome are presented to theclinician. Still further, where a treatment regimen of multipledifferent treatments are identified these too are presented to theclinician in the personalized plan 612. Further, for each treatmentoption, specific details of frequency, power, duration, dosage,co-treatment options, and others may be presented to enable theselection of a very detailed treatment plan to best treat the patient“P,” based on the data recorded in database 500 of prior treatmentshaving the most successful outcomes for patients with the most similardiseases, disease states, and other correlated data between the patient“P” and the prior patients' data stored in database 500.

Additionally, sorting or ranking of treatment options may also be basedon specific tumor type and subtypes, genetic mapping of tumor and othernon-cancerous tissue, by disease stage and location, by similar pooledpatient's including data such as race, ethnicity, age, family history,reported treatment outcomes by specific treatment type, outcomesincluding overall progression free survival, overall survival, time torecurrence and/or resistance, and type of resistance (mutation type).Further, data may also be sorted in reverse, where data is filteredbased on gene mutations, treatments and outcomes. In such cases, theoutput is determining who response best (which age group, race group,ethnic group, family history group, etc.), and of which whole genomesequencing is conducted (on non-tumorous tissue) to identify cancer andnon-cancer related genes to help understand prognosis/diseasemechanisms.

As a further alternative, the database 500 may be searchable directly bythe clinician, enabling them to make their own assessments, either withor without software parameter limitations. For example, the clinicianmay perform a search using a form (not shown) where the clinician inputsor selects the data which is determined most important. In one instancethis may be pathology, gene profile, and age of the patient. The resultsof this simple inquiry will enable the clinician to review both thetreatments and outcomes for similarly aged individuals having the samecytological and/or gene profile as the patient “P.” With this data theclinician and the care team can make assessments of how best to proceedfor patient “P.” Alternatively, the software may consider the inquiryand simply report back the ranked treatment options and expectedtreatment outcome for each based on the inquiry. As will be appreciated,the greater the degree of similarity between prior patients and thecurrent patient “P,” the greater the confidence that a treatment with asuccessful outcome can be repeated in patient “P.” Thus, the ability forthe clinician to consider the recommendations of the software and thenlook at the underlying data and make additional comparisons may be veryuseful. The software enables the entire file of the prior patientsidentified as analogues to be reviewed by the clinician to considerwhether an identified analogue should be included or excluded from thegroup used to develop the personalized plan. As will be appreciated, thedata in database 500 that is searchable by clinicians, with theexception of patient data for those patients under the care of aparticular physician will be scrubbed of identification data andincapable of revealing information in conflict with privacy protectionrules.

Web page 600 in FIG. 6 also includes a tab 614 connecting the clinicianto literature and other information that might be relevant to theclinician in assessing the diagnosis and developing the personalizedplan 612. This might include treatment protocols, potential side effectsof a particular treatment, and others. This data may be resident indatabase 500 or the software operating on server 212 may direct theclinician to an appropriate location where the information isaccessible, for example the website for the National Institute of Health(U.S.) or the National Health Service (U.K.), or other relevantrepositories of such information.

Following review of all the available data described above in connectionwith step 132 and web page 600, the care team decides on a particulartreatment plan, as embodied in field 612, which is stored in database500, and then effectuated. Treatment occurs in step 134.

In one example, microwave ablation catheter 324 is inserted into EWC318, and into the target and microwave ablation energy is applied totreat the target. A variety of power settings, durations, cycleinformation, and other treatment options may be employed to mosteffectively treat the tumor without unnecessarily affecting adjacenttissue. In addition a variety of co-treatment options may be followedincluding, following the ablation with chemotherapy, radiation, or othertherapies. The occurrence of the treatment 134 is recorded into database500, including any relevant factors relating to the treatment. Forexample, if it is determined that the treatment is to be via microwaveablation, other factors might include power, duration, number of cyclesof treatment, number of sites treated, etc. Similarly, if the treatmentis via surgery additional factors included might be approach to site(anterior or posterior), duration of surgery, etc. Or if a combinationof treatments, the type of drug therapy and dosage and the relevantradiation parameters. Again these data are recorded in database 500 forinclusion both in the record of the individual patient “P” and forcomparison and use in developing a treatment plan for subsequentpatients.

Following treatment 134, and storing the treatment data to the database500 at step 136, a patient will typically have a regimented follow-upreview with their doctor to observe the effectiveness of the treatmentallowing for outcome monitoring 138 to be conducted. This may includeimaging of the target that was treated. These images will be stored indatabase 500 to make them available to both the care team for thepatient “P,” as well as allowing the effectiveness of a treatment to beconsidered by other clinicians when making treatment decisions for theirpatients, as described above with respect to step 132. The images takenas part of the follow-up observations may be stored in database 500along with other observations of the treatment by the clinicianincluding challenges for the patient such as nausea, weakness, hairloss, etc., so that all of this empirical data of the treatments can bemade available and considered by these other patients and theirphysicians.

These outcome monitoring steps 138 may be separate from, or may be partof, steps 102-106, when a patient undergoes these steps for the secondand subsequent times. The result is a continuum of care for a patient,where their specific treatment is personalized for them and based on thewidest possible knowledge that affects them specifically and theircancer specifically, but further is made available for other patientsand clinicians to consider in their treatment of other patients.

A further benefit of this continuum of treatment is the gathering ofstatistical data relating to the frequency and timing of mutations oflesions. Each time either cytopathology or a gene profile test isconducted an additional data point for the disease in question iscaptured. This data can be aggregated in the database to determine ifthere is any regularity to the changes and mutations of the disease.Further, likelihood of mutation can be assessed in view of theadditional data. For example, it may be determined that a massdiscovered in a geriatric patient, even if left untreated, will notsignificantly mutate or change into a more deadly form that wouldsignificantly impact the life expectancy of the patient, whereas thesame mass expressing the same genetic and cytological profile in a childcan be expected to mutate and progress rapidly and thus require a verydifferent course of action.

Further, the data stored in database 500 may define correlations betweenan early detected mass and a late stage cancer which were heretoforeunknown. This correlation allows for greater level of positive outcomesto be achieved by better defining those presentations that requireimmediate aggressive treatment, even if currently benign, as compared tothose presentations that can accept a more graduated treatment regimenwithout an increased likelihood of mortality.

Described herein are a few options for retrieving samples of a targetand treating the disease. The EMN system 300 is particularly useful forbiopsy sampling via biopsy needles or forceps. In addition, the use ofthe EMN system 300 for microwave ablation of the target using a flexiblemicrowave catheter 324 as depicted in FIG. 3 is also contemplated.However, other known techniques are also contemplated within the scopeof the present disclosure for both data generation and treatment. Forexample, it is known that tumorous tissue generally has a differentcellular structure and composition than surrounding tissue. As a result,tumors and lesions exhibit a different spectroscopic response thanhealthy tissue, that is, the tumorous tissue emits energy differentlythan the surrounding tissue. As a result, this difference inspectroscopic response can be measured and used to provide greaterclarity with respect to the location, meets and bounds of the tumor, andguarantee of placement. In this respect the tumor or lesion has aspectroscopic fingerprint which can be used to distinguish the tumor orlesion from surrounding tissue. Accordingly, one embodiment of thepresent disclosure employs the use of an electromagnetic signal emitter(e.g., microwave, infrared, etc.) emitting a signal at a non-treatmentlevel. The tumor or lesion will absorb the signal (as will the healthytissue) but the tumor or lesion will emit a very different response tothis energy than the healthy tissue. This difference in response (e.g.,the emittance of absorbed energy) can be measured using a receiver(e.g., a microwave antenna or a fiber optic strand) and the receivedsignal analyzed to distinguish tissue. This received signal of emittancecan then be saved in the database 500 for yet another data pointregarding that tumor which may be useful in follow-up procedures for thespecific patient as well as for comparative purposes for other patients'diseases. In one aspect of the present disclosure this “spectroscopicfingerprint” can be used to provide either guidance to cytopathologistsor as a confirmation of the cytopathological results. Further, asgreater data is collected and the confidence interval of spectroscopicfingerprints increases, a clinician may have sufficient confidence insuch data that treatment may be commenced based on this data even priorto receiving the cytopathological and genetic testing results.

Yet a further embodiment of the present disclosure relates to the use ofmarkers. As described above, fiducial markers, both real and virtual,can be placed in the patient or the image data file during use of theEMN system 300. However, a variety of other types of markers may also beemployed without departing from the scope of the present disclosure. Forexample, following genetic testing, it may be determined that thedesired course of action is a “watchful waiting” approach. In such ascenario it can be desirable to isolate, to the extent possible, thetumor from the healthy tissue. One method of achieving this is to employa cross-linking agent which has a particular affinity to a particulargene mutation. These materials can be injected into the tumor via thebiopsy needle, and over time will cross-link to essentially harden themass or tumor. This may be beneficial to enable palpation of the tumor,or to increase its visibility. In one aspect of the present disclosure,the cross-linking agent has a coloring agent associated with it, forexample, a fluoroscopic dye or an autofluorescent dye. These techniquesalso make the tumor or mass easier to find in subsequent EMN proceduresand enable visualization of the tumor. Other materials that may beutilized to isolate the tumor from surrounding tissue and make it easierto identify include magnetic particles compositions which stain thetumor.

Although embodiments have been described in detail with reference to theaccompanying drawings for the purpose of illustration and description,it is to be understood that the inventive processes and apparatus arenot to be construed as limited. It will be apparent to those of ordinaryskill in the art that various modifications to the foregoing embodimentsmay be made without departing from the scope of the disclosure.

1. A method of assessing a target comprising: collecting patient data;identifying a target in an image dataset; preparing a pathway plan toarrive at the target; inserting a medical instrument and following thepathway plan to arrive at the target from an opening; extracting a firstbiopsy sample from the target; performing a cytopathological examinationon the biopsy sample; collecting genetic information from the biopsysample; and presenting one or more treatment options based on acorrelation of the patient data, the cytological examination, and thegenetic information of the first biopsy sample, and their comparison tothe patient data, cytological examination and genetic information ofpreviously acquired biopsy samples.
 2. The method of claim 1, whereinthe presentation of the treatment options includes presentation ofdetails of the first biopsy sample including one or more of the imagesfrom the image dataset, the cytopathological examination results, andthe genetic information.
 3. The method of claim 1, wherein the priorbiopsy samples are from the same target.
 4. The method of claim 1,wherein the prior biopsy samples are from a different target in the samepatient.
 5. The method of claim 1, wherein the prior biopsy samples arefrom a different patient.
 6. The method of claim 1, wherein thecorrelation identifies a similarity in the cytological examinationresults of the first biopsy sample and the previously acquired biopsysamples.
 7. The method of claim 1, wherein the correlation identifies asimilarity of gene mutation of the first biopsy sample and thepreviously acquired biopsy samples.
 8. The method of claim 1, whereinthe correlation identifies a similarity of one or more of cytologicalexamination results, a gene mutation, age, ethnicity, sex, infirmity ofpatient, location of the target, and observed outcomes in the firstbiopsy sample and the previously acquired biopsy samples.
 9. The methodof claim 1, wherein the presented treatment options includes thestandard of care, clinical trials, and investigational treatments. 10.The method of claim 1, wherein the presented treatment options includean expected outcome, the expected outcome based on observed outcomesstored in the database related to the prior biopsy samples used in thecorrelation.
 11. The method of claim 10, wherein the presented treatmentoptions include treatment details including one or more of power,intensity, dosage, duration, number of cycles, treatment regimen,co-treatments, and timing of each.
 12. The method of claim 1, whereinthe database stores the patient data, the image data, the cytologicalexamination results, and the genetic information in a databaseaccessible via a network.
 13. The method of claim 12, wherein thepresented treatment options are accessible to a care team via a network.14. The method of claim 12, wherein upon selecting a treatment option,the selected treatment option is stored in the database.
 15. The methodof claim 14, wherein upon executing the selected treatment, thetreatment details are stored in the database including one or more ofpower, intensity, dosage, duration, number of cycles, treatment regimen,co-treatments, and timing of each.
 16. The method of claim 14, furthercomprising observing the outcome of the selected treatment and storingdata related to the outcome in the database.
 17. The method of claim 16,wherein, following observing the outcome of the selected treatment, thedata stored in the database for the patient is available to others forconducting a different correlation for a biopsy sample taken from adifferent patient.
 18. The method of claim 16, wherein observing theoutcome includes generating a second image data set and storing thesecond image data set in the database.
 19. The method of claim 17,wherein the second image data set depicts one or more markers placed inthe patient during the biopsy extraction.
 20. The method of claim 17,further comprising: acquiring a second biopsy sample; performing acytological examination on the second biopsy sample; collecting geneticinformation of the second biopsy sample; and presenting one or moretreatment options based on a correlation of the patient data, thecytological examination, and the genetic information of the secondbiopsy sample, and their comparison to the patient data, cytologicalexamination and genetic information of previously acquired biopsysamples.